Associations between Single-Nucleotide Polymorphisms in Corticotropin-Releasing Hormone-Related Genes and Irritable Bowel Syndrome

PLoS One. 2016 Feb 16;11(2):e0149322. doi: 10.1371/journal.pone.0149322. eCollection 2016.


Irritable bowel syndrome (IBS) is a common functional disorder with distinct features of stress-related pathophysiology. A key mediator of the stress response is corticotropin-releasing hormone (CRH). Although some candidate genes have been identified in stress-related disorders, few studies have examined CRH-related gene polymorphisms. Therefore, we tested our hypothesis that single-nucleotide polymorphisms (SNPs) in CRH-related genes influence the features of IBS.

Methods: In total, 253 individuals (123 men and 130 women) participated in this study. They comprised 111 IBS individuals and 142 healthy controls. The SNP genotypes in CRH (rs28364015 and rs6472258) and CRH-binding protein (CRH-BP) (rs10474485) were determined by direct sequencing and real-time polymerase chain reaction. The emotional states of the subjects were evaluated using the State-Trait Anxiety Inventory, Perceived Stress Scale, and the Self-rating Depression Scale.

Results: Direct sequencing of the rs28364015 SNP of CRH revealed no genetic variation among the study subjects. There was no difference in the genotype distributions and allele frequencies of rs6472258 and rs10474485 between IBS individuals and controls. However, IBS subjects with diarrhea symptoms without the rs10474485 A allele showed a significantly higher emotional state score than carriers.

Conclusions: These results suggest that the CRH and CRH-BP genes have no direct effect on IBS status. However, the CRH-BP SNP rs10474485 has some effect on IBS-related emotional abnormalities and resistance to psychosocial stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Corticotropin-Releasing Hormone / genetics*
  • Depression / genetics
  • Female
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Irritable Bowel Syndrome / genetics*
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Psychometrics
  • Sex Characteristics
  • Young Adult


  • Carrier Proteins
  • corticotropin releasing factor-binding protein
  • Corticotropin-Releasing Hormone

Grant support

This research was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan No. 15H04799, 15H15267 ( and Grant-in-Aid for Scientific Research from the Ministry of Health, Welfare, and Labor of Japan (26-4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.